The long-term objective of the proposed studies is to determine whether gestational B(a)P exposure[unreadable] nterferes with normal behavior and neural function in C57BL mice as demonstrated by significant deficits in[unreadable] "lippocampal synaptic plasticity and behavior. The central hypothesis to be tested is that gestational[unreadable] exposure to B(a)P aerosol (PM2.5mu) at levels seen in humans in certain environments result in lifelong[unreadable] learning and memory deficits, and that these deficits that are mediated, at least in part, through modulation[unreadable] of developmental NMDA/AMPA glutamate receptor subunit expression and function at a time when[unreadable] excitatory synapses are being formed in the hippocampus of C57BL mice. AIM #1 will determine the[unreadable] disposition of B(a)P in F1 fetal brain (in C57BL mice) on gestational day (GD) 14, 16, 18, and postnatal day[unreadable] (PND) 0 in the hippocampus after GD14-17 inhalation exposure at doses of 0, 50, 100 and 200 mu g/m3A[unreadable] simultaneous determination of the effect on glutamate receptor subunit expression in utero will be[unreadable] conducted, using ex vivo primary neuronal cultures. AIM #2 will test whether gestational exposure to the[unreadable] same inhalational doses of B(a)P results in deficits in learning, using behaviors previously shown to depend[unreadable] on hippocampal function. AIM #3 will correlate gestational exposure to B(a)P with measures of hippocampal[unreadable] long-term potentiation (LTP), evaluated at PND 60 and 120 in F1 generation mice. The involvement of[unreadable] NMDA and/or, AMPA receptors in this LTP, and its changes due to B(a)P exposure, will be assessed by[unreadable] application of NMDA or AMPA-selective receptor antagonists prior to LTP analysis of control and B(a)P[unreadable] exposed F1 generation mice. AIM #4 will test whether gestational exposure to the doses of B(a)P which[unreadable] lead to behavioral learning and physiological deficits also modulate the expression of various NMDA and[unreadable] AMPA receptor subnits, profiled for expression levels on GD18 and PND 0, 5, 10, 20, and 60 using real time[unreadable] PCR (for mRNA assessment) and Western blot analyses( for subunit protein assessment) in control and[unreadable] B(a)P exposed F1 generation C57BL mice. These studies will serve as the first step in querying the with the[unreadable] causality of altered glutamate receptor subunit expression subsequent to gestational exposure to B(a)P in[unreadable] attenuation of learning behaviors in adult animals, which will be extended in future studies by exploiting mice[unreadable] genetically altered to modify the expression of relevant AMPA or NMDA receptor subunits, or their[unreadable] downstream effector molecules. These studies are directly relevant to human consequences of B(a)P[unreadable] exposure, and we anticipate that our studies will lead to the rigorous characterization of an important animal[unreadable] model both to understand the etiology of environmental toxin-induced neurological dysfunction and to test[unreadable] hypotheses regarding effective therapeutic or other interventions .